Localization of hepatocyte growth factor activator inhibitor type 1 in Langhans' cells of human placenta

Abstract

Activation of hepatocyte growth factor (HGF) is a crucial limiting step in HGF-induced signaling pathway. The HGF activator inhibitor type 1 (HAI-1) was identified as a potent inhibitor of HGF activator (HGFA), a serine proteinase that is responsible for the activation of HGF in vivo. HAI-1 is an integral membrane Kunitz-type serine proteinase inhibitor, and its mRNA has been reported to be most abundant in the placenta. In this report, specific antibody to HAI-1 was used in an immunohistochemical procedure to determine the localization of HAI-1 in human placenta. HAI-1 was expressed in cytotrophoblasts (Langhans' cells) of the double-layered trophoblastic epithelium of chorionic villi tissue, and syncytiotrophoblasts were almost negative. On the other hand, extravillous trophoblasts of cytotrophoblastic columns showed markedly decreased immunoreactivity, and those infiltrating into the superficial decidua membrane of early placenta were hardly stainable. The amnionic epithelial cells were also immunostained intensely. The presence of HAI-1 mRNA was also confirmed in a cultured human cytotrophoblastic cell line. In addition to HAI-1, low but distinct expression of HGFA mRNA was observed in the placenta tissue and cultured cytotrophoblasts by using a sensitive RT-PCR method. Since HGF plays an essential role in the placenta development, expression of HAI-1 and HGFA may have an important regulatory role in the placenta. The localization of HAI-1 in the proliferating trophoblastic stem cells (Langhans' cells), but not in syncytiotrophoblasts and extravillous trophoblasts, suggest a possible role of HAI-1 in the proliferation of trophoblasts.

Emerging multifunctional aspects of cellular serine proteinase inhibitors in tumor progression and tissue regeneration

“…In the placenta, where HAI-1 mRNA is most abundantly present, cytotrophoblasts and the epithelial cells of the amnionic membrane are strongly stained. 115 The immunohistochemical study also confirmed the injury-and regeneration-induced HAI-1 upregulation in the various epithelial tissues, such as the gastrointestinal mucosa, renal tissue and liver, 114 suggesting that HAI-1 is possibly involved in the survival and regeneration of the epithelial tissue. Various types of carcinoma cells also express HAI-1 immunohistochemically.…”

Deregulated matriptase activity in oral squamous cell carcinoma promotes the infiltration of cancer‐associated fibroblasts by paracrine activation of protease‐activated receptor 2

“…Subsequent studies revealed that membrane‐associated serine proteases with trypsin‐like activity are primary targets of both HAIs . HAI‐1 is expressed by most epithelial cells and placental trophoblasts, and its most important cognate protease on the epithelial cell surface is matriptase, a type II transmembrane serine protease (TTSP). Other TTSPs such as hepsin, human airway trypsin‐like protease and TMPRSS13, as well as a glycosylphosphatidylinositol‐anchored serine protease prostasin, are also sensitive to HAI‐1 .…”

Changes in plasma levels of hepatocyte growth factor and its associated factors during pregnancy

“…At present we do not know the reason why HAI‐1 levels in the maternal plasma increased as pregnancy progressed. During pregnancy, HAI‐1 is produced mainly from placental villous cytotrophoblasts 19 . Morphological study showed that total number of cytotrophoblasts cells in the pregnant patients increased steadily until term 20 .…”